Diaryl ether (DE) is a functional scaffold existing widely both in natural products (NPs) and synthetic organic compounds. Statistically, DE is the second most popular and enduring scaffold within the numerous medicinal chemistry and agrochemical reports. Given its unique physicochemical properties and potential biological activities, DE nucleus is recognized as a fundamental element of medicinal and agrochemical agents aimed at different biological targets. Its drug-like derivatives have been extensively synthesized with interesting biological features including anticancer, anti-inflammatory, antiviral, antibacterial, antimalarial, herbicidal, fungicidal, insecticidal, and so on. In this review, we highlight the medicinal and agrochemical versatility of the DE motif according to the published information in the past decade and comprehensively give a summary of the target recognition, structure–activity relationship (SAR), and mechanism of action of its analogues. It is expected that this profile may provide valuable guidance for the discovery of new active ingredients both in drug and pesticide research.

Whereas most conventional DNA probes are flat disklike aromatic molecules, we explored the possibility of developing quadruplex sensors with nonplanar conformations, in particular, the propeller-shaped tetraphenylethene (TPE) salts with aggregation-induced emission (AIE) characteristics. 1,1,2,2-Tetrakis[4-(2-triethylammonioethoxy)phenyl]ethene tetrabromide (TPE-1) was found to show a specific affinity to a particular quadruplex structure formed by a human telomeric DNA strand in the presence of K(+) ions, as indicated by the enhanced and bathochromically shifted emission of the AIE fluorogen. Steady-state and time-resolved spectral analyses revealed that the specific binding stems from a structural matching between the AIE fluorogen and the DNA strand in the folding process. Computational modeling suggests that the AIE molecule docks on the grooves of the quadruplex surface with the aid of electrostatic attraction. The binding preference of TPE-1 enables it to serve as a bioprobe for direct monitoring of cation-driven conformational transitions between the quadruplexes of various conformations, a job unachievable by the traditional G-quadruplex biosensors. Methyl thiazolyl tetrazolium (MTT) assays reveal that TPE-1 is cytocompatible, posing no toxicity to living cells.

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Butyrylcholinesterase (BChE) is widely distributed in various tissues and highly implicated in several important human diseases, especially Alzheimer's disease (AD). However, the role of BChE in AD is still controversial, which may be partially attributed to the lack of a direct tool for real-time and noninvasive monitoring of BChE in in vivo. Here, we report three rationally designed near-infrared fluorogenic probes that possess excellent discrimination for butyrylcholinesterase (BChE) over the related enzyme acetylcholinesterase (AChE). The refined probe, BChE-NIRFP, not only functions as an exquisite substrate for BChE in in vitro assays but also represents a superb "signal-on" imaging tool to real-time track BChE levels in human cells, zebrafish, and a mouse model of AD. A further application of BChE-NIRFP to identify the cellular mechanism reveals that Aβ fibrils and insulin resistance may be important contributors to the abnormally elevated BChE levels observed during AD progression. Based on the results from the present study, this new probe is a valuable tool for basic and clinical research designed to obtain a complete understanding of the physiological roles of BChE in diverse human diseases, particularly AD.